Autism is thought to be associated with abnormal hemispheric specialization and left-hemispheric dysfunction. Brain functional imaging using 133Xe-SPECT (single photon emission computed tomography) was used to measure left/right asymmetry and absolute values of regional cerebral blood flow (rCBF) in 18 children with autism aged from four to 17 years and 10 age-matched controls. All controls but only 10 children with autism were right-handed. The left-to-right indices, both hemispheric and regional, were positive in controls, indicating higher left than right rCBF values, but were negative in patients with autism. This inversion was statically significant for total hemispheres, sensorimotor and language-related cortex and was explained by a significant decrease of the left absolute rCBF values in these regions in the patients with autism. The inversion was independent of handedness, sex and age. These results confirm the existence of left-hemispheric dysfunction in childhood autism, especially in the cortical areas devoted to language and handedness, leading to anomalous hemispheric specialization.